The natural killer (NK) gene complex (NKC) encodes orphan lectin-like NK cell receptors that may explain uncharacterized NK cell specificities. Unlike other NKC-encoded receptors that recognize molecules with major histocompatibility complex (MHC) class I folds, here we show that mouse Nkrp1d and Nkrp1f bind specific C-type lectin-related (Clr) molecules. Nkrp1d mediated inhibition when recognizing Clrb, a molecule expressed in dendritic cells and macrophages. Nkrp1 (official gene name, Klrb1) and Clr are intertwined in a genetically conserved NKC region showing recombination suppression, reminiscent of plant self-incompatibility loci. Thus, these findings broaden the 'missing-self' hypothesis from solely involving MHC class I to including related NK cell receptors for lectin-like ligands, and reflect genetic strategies for biological self-recognition processes in other species.